Jan. 7, 2016
Unethical Medical Experiment at Three VA Hospitals Increased Risk of Heart Attacks and Other Complications
Public Citizen Calls for Veterans Affairs Investigation Into Clinical Trial That Needlessly Put Patients at Risk
WASHINGTON, D.C. – Public Citizen is sounding the alarm about a clinical drug trial that needlessly threatened the lives of subjects assigned to the control group. In addition, participants in the trial may not have been informed about the risks – which would be a clear violation of rules designed to protect human subjects, Public Citizen said.
Today, Public Citizen sent a letter (PDF) to the Office of Research Oversight (ORO) at the U.S. Department of Veterans Affairs (VA) asserting that the CHAMPION PHOENIX trial unnecessarily increased the risk of death, heart attack and other adverse cardiac events for subjects placed in the control group.
The trial was conducted at 153 institutions around the world, including three VA facilities: the Dallas VA Medical Center, the Jesse Brown VA Medical Center in Chicago and the VA Boston Healthcare System. The study involved more than 11,000 subjects, 84 of whom were patients at the three VA medical centers.
The primary goal of the trial was to determine whether an experimental intravenous antiplatelet medication known as cangrelor is more effective at preventing death, heart attacks and other serious cardiac complications than the standard-of-care oral antiplatelet medication clopidogrel in patients undergoing coronary artery stent procedures. The increased risk to control group subjects resulted from failure to ensure they were treated with clopidogrel prior to their coronary stent procedures.
A coronary stent is a tiny metal mesh tube that is placed in an artery supplying blood to the heart to keep the artery open, as well as to improve or maintain circulation. Stents often are placed in patients who have suffered a recent heart attack or are experiencing chest pain due to low blood supply to the heart.
One potential complication of these procedures is the formation of a blood clot inside the stent – which can lead to a heart attack, cardiac arrest, the need for emergency procedures to remove the clot and even death. Patients undergoing coronary artery stent procedures routinely receive antiplatelet medication to prevent these dangerous clots.
An analysis by a senior medical reviewer at the U.S. Food and Drug Administration found that failure to administer the necessary antiplatelet treatment occurred in 89 percent of subjects enrolled at the three VA facilities compared with 30 percent of subjects enrolled at non-VA facilities.
“The seriously flawed trial protocol paved the way for inappropriate and shocking delays in antiplatelet therapy for subjects enrolled in the control group at all trial institutions,” said Dr. Michael Carome, director of Public Citizen’s Health Research Group. “Inexplicably, the rate of such delays was extraordinarily high at the VA trial sites, making participation in the trial even more hazardous for subjects randomized to the control group at those sites compared with other sites.”
Public Citizen’s complaint contends that the trial’s research protocol was unethical because it failed to require that control group subjects receive lifesaving antiplatelet medications as soon as possible prior to undergoing coronary artery stent procedures.
Prior research conducted by the same research team, expert clinical practice guidelines and other data available to the researchers established that withholding clopidogrel until after the coronary stent procedures constitutes substandard care. Indeed, one of the two lead researchers for the trial stated publicly before the trial’s initiation, “If you ask the experts, they will all tell you to give antiplatelet therapy up front before the PCI [coronary stent] procedure.”
Public Citizen is calling on the ORO to investigate why the institutional review boards responsible for reviewing human research at the three VA medical facilities approved the trial given a design that was unethical and failed to minimize the risks to the control group subjects. The complaint also urges the ORO to investigate whether proper consent of the subjects was obtained in light of the risks, as required by the VA’s human subjects protection rules.
Another key issue that requires further inquiry – but falls outside the scope of the ORO’s jurisdiction – is whether inappropriate delays in antiplatelet therapy were more widespread at VA health care facilities for patients who did not participate in the trial. Public Citizen, in a separate letter (PDF), is urging the VA’s Office of Inspector General to promptly launch an investigation to find out.